Glucose counterregulation in advanced type 2 diabetes: effect of ß-adrenergic blockade.

ABSTRACT

OBJECTIVE: To examine counterregulatory glucose kinetics and test the hypothesis that ß-adrenergic blockade impairs these in patients with type 2 diabetes mellitus (T2DM) and advanced ß-failure. RESEARCH DESIGN AND METHODS: Nine insulin-requiring T2DM subjects and six matched nondiabetic control subjects were studied. ß-Cell function was assessed by the C-peptide response to arginine stimulation. Counterregulatory hormonal responses and glucose kinetics were assessed by hyperinsulinemic euglycemic-hypoglycemic clamps with [3-(3)H]glucose infusion. T2DM subjects underwent two clamp experiments in a randomized crossover fashion once with infusion of the ß-adrenergic antagonist propranolol and once with infusion of normal saline. RESULTS: Compared with the control subjects, T2DM subjects had threefold reduced C-peptide responses to arginine stimulation. During the hypoglycemic clamp, glucagon responses were markedly diminished (16.0 ± 4.2 vs. 48.6 ± 6.0 ng/L, P < 0.05), but other hormonal responses and the decrement in the required exogenous glucose infusion rate (GIR) from the euglycemic clamp were normal (-10.4 ± 1.1 vs. -7.8 ± 1.9 µmol · kg(-1) · min(-1) in control subjects); however, endogenous glucose production (EGP) did not increase (-0.8 ± 1.0 vs. 2.2 ± 0.7 µmol · kg(-1) · min(-1) in control subjects, P < 0.05), whereas systemic glucose disposal decreased normally. ß-Adrenergic blockade in the T2DM subjects increased GIR ∼20% during the euglycemic clamp (P < 0.01), but neither increased GIR during the hypoglycemic clamp or decreased its decrement from the euglycemic clamp to the hypoglycemic clamp. CONCLUSIONS: Overall glucose counterregulation is preserved in advanced T2DM, but the contribution of EGP is diminished. ß-Adrenergic blockade may increase insulin sensitivity at normoglycemia but does not impair glucose counterregulation in T2DM patients, even those with advanced ß-cell failure.